scholarly journals A Circulating Tumor Cell-RNA Assay for Assessment of Androgen Receptor Signaling Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer

Theranostics ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 2812-2826 ◽  
Author(s):  
Yu Jen Jan ◽  
Junhee Yoon ◽  
Jie-Fu Chen ◽  
Pai-Chi Teng ◽  
Nu Yao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cell ◽  
Circulating Tumor Cell ◽  
Receptor Signaling ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Signaling ◽  
Castration Resistant

A circulating tumor cell specific RNA assay for assessment of androgen receptor signaling inhibitor sensitivity in metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5059-5059
Author(s):  
Pai-Chi Teng ◽  
Yu Jen Jan ◽  
Junhee Yoon ◽  
Pin-Jung Chen ◽  
Jie-Fu Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Androgen Receptor ◽  
Tumor Cell ◽  
Cell Lines ◽  
Circulating Tumor Cell ◽  
Z Score ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Signaling ◽  
Castration Resistant

5059 Background: Our objective is to develop a circulating tumor cell (CTC)-RNA assay for characterizing clinically relevant RNA signatures for the assessment of androgen receptor signaling inhibitors (ARSIs) sensitivity in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We developed NanoVelcro CTC-RNA Assay by combining Thermoresponsive(TR)-NanoVelcro CTC purification system with NanoString nCounter platform for CTC purification and RNA analysis. Based on the well-validated, tissue-based Prostate Cancer Classification System (PCS), we selected the most aggressive and ARSI-resistant subtype- the PCS1, for CTC analysis. We applied a rigorous bioinformatic process to develop a CTC-PCS1 panel that is specific to PC CTCs. We validated NanoVelcro CTC-RNA Assay and CTC-PCS1 panel with PC cell lines to demonstrate sensitivity and specificity of the PCS1 Z score (the likelihood estimate of the PCS1 subtype) for identifying PCS1 subtype and ARSI resistance. We then selected 31 blood samples from 23 PC patients receiving ARSIs to test in our assay. The PCS1 Z score of each sample was computed and compared with ARSI treatment sensitivity. Results: We established a 16-gene CTC-PCS1 panel that consists of CTC-specific RNA signatures. The validation studies using PC cell lines showed that the assay can detect the RNA transcripts with high sensitivity and scalability in the range of 1-100 cells. We also showed that the genes in CTC-PCS1 panel is highly expressed in PC cells. We further demonstrated that the CTC-PCS1 panel is highly specific in identifying PCS1-like samples, and the high PCS1 Z score is associated with ARSI resistance. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). In 8 patients who were initially sensitive to ARSI (ARSI-S) and later developed resistance (ARSI-R), we found that the PCS1 Z score increased from the time of ARSI-S to the time of ARSI-R (Pairwise T-test, P=0.016). Conclusions: Using our new methodology, we developed a first-in-class CTC-RNA assay and demonstrated the feasibility of transforming clinically-relevant tissue-based RNA profiling into CTC tests. This approach allows for detecting RNA expression relevant to clinical drug resistance in a non-invasive fashion, which can facilitate patient-specific treatment selection and early detection of drug resistance- a goal in precision oncology.

scholarly journals Adaptive responses of androgen receptor signaling in castration-resistant prostate cancer

Oncotarget ◽  
2015 ◽  
Vol 6 (34) ◽  
pp. 35542-35555 ◽  
Author(s):  
Sven Perner ◽  
Marcus V. Cronauer ◽  
Andres Jan Schrader ◽  
Helmut Klocker ◽  
Zoran Culig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Receptor Signaling ◽  
Castration Resistant Prostate Cancer ◽  
Adaptive Responses ◽  
Androgen Receptor Signaling ◽  
Castration Resistant

scholarly journals Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 352 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh Sikka
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Inflammatory Response ◽  
Pivotal Role ◽  
Receptor Signaling ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Signaling ◽  
Critical Pathways ◽  
Castration Resistant

Oxidative stress, inflammation and androgen receptor (AR) signaling play a pivotal role in the initiation, development and progression of prostate cancer (PCa). Numerous papers in the literature have documented the interconnection between oxidative stress and inflammation; and how antioxidants can combat the inflammation. It has been shown in the literature that both oxidative stress and inflammation regulate AR, the key receptor involved in the transition of PCa to castration resistant prostate cancer (CRPC). In this review, we discuss about the importance of targeting Nrf-2-antioxidant signaling, NF-κB inflammatory response and AR signaling in PCa. Finally, we discuss about the crosstalk between these three critical pathways as well as how the anti-inflammatory antioxidant phytochemicals like sulforaphane (SFN) and curcumin (CUR), which can also target AR, can be ideal candidates in the chemoprevention of PCa.

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